19 Immune Tolerance

Question 1

What is meant by immune tolerance?

Answer 1

Unresponsive ness to an antigen due to previous exposure to the antigen

Question 2

What is meant by autoimmunity

Answer 2

Destruction of self antigens by the body

Question 3

How is immune tolerance completed?

Answer 3

The B and T cells that express self antigens must be downgraded or destroyed. Several mechanisms are involved in this including central and peripheral response

Question 4

How does central tolerance develop?

Answer 4

The thymus plays a big role in eliminating T cells with high affinity to self antigens. Bone marrow is important in B cell tolerance o

Question 5

What occurs during peripheral tolerance?

Answer 5

Mature lymphocytes that recognise self antigens in peripheral tissue become incapable of activation or die by apoptosis

Question 6

What are the mechanisms of immunological tolerance?

Answer 6

Anergy- functional unresponsiveness
Antigen- recognition with co-stimulation
Treg suppression
Deletion(cell death)
Some self antigens are sequestered from the immune system by anatomic barriers

Question 7

How can molecules overcome peripheral tolerance?

Answer 7

Inappropriate of self antigens
Inappropriate or increased local expression of co-stimulatory molecules
Alterations in the way self molecules are presented to the immune system
More likely to happen during inflammation or cell damage
Self peptides can be altered by virus’, free radicals or ionising radiations

Question 8

What contributes to autoimmune disease?

Answer 8

Genetics
Infection
Environmental factors

Question 9

What are natural antibodies?

Answer 9

B1 cells secrete natural antibodies, these can cross react with a and B blood groups to destroy blood not of that type

Question 10

What contributes to T cells not being able to broken down properly

Answer 10

Inherited HLA that is damaged and won’t recognise self antigens
Poor expressions of self antigens in the thymus
Infections
Drugs

Question 11

What genetic factors cause autoimmune disease?

Answer 11

Clusters within families of certain polymorphisms that increases the chance of these diseases

Question 12

What is AI-RE?

Answer 12

Autoimmune regulator acts to eliminate T cells, in its abscence self antigen T cells can be eliminated

Question 13

What environmental factors cause autoimmunity?

Answer 13

Drugs-molecular mimicry, up regulation of co stimulation,

Viruses- molecular mimicry, genetic variation in drug metabolism

UV radiation- trigger for skin inflammation, modification of self antigen

Question 14

Give some examples of molecular mimicry?

Answer 14

Group A strep- antigen found in cardiac muscle, can lead to rheumatic fever

Coxsackie B4 nuclear protein- pancreatic islet cell gultamate decarboxylase leads to type 1 diabetes

Campylobacter jejuni glycoproteins- myelin associated gangliosides and glycolipids- leads to guillian Barre syndrome

Question 15

How does infection lead to autoimmunity?

Answer 15

Antigen presenting cells are activated, expressing c stimulation. This may cause self antigens to react due to molecular mimicry

Question 16

Give some examples of hormone receptors that cause autoimmune disease

Give some examples of neurotransmitter receptors that are affected by autoimmune disease?

Answer 16

TSH receptrors–> hyperthyroidsim or hypothyroidism
Insulin receptors–> hyper/hypoglycaemia

Acetylcholine receptors-myasthenia gravis

Question 17

Give some examples of cell adhesion molecules that are affected by autoimmune diseases

Give some examples of plasma proteins that can be affected by autoimmune disease

Give some examples of Other cell surface antigens that can be affected by autoimmune disease

Answer 17

Epidermal cell adhesion molecules–> blistering skin disease

Factor VIII- acquried heamophilia
Beta-2 glycoprotein I and other anticoagulant proteins

Red blood cells (multiple antigens)–>heamolytic anaemia
Platelets–> thrombocytopenia purpura

Question 18

Give some examples of intracellular enzymes that cause autoimmune disease?

Answer 18

Thyroid peroxidase- thyroiditis, hypothyroidism

Steroid 21-hydroxylase (adrenal cortex)- adrenocortical failure (addisons)

Glutamate decarboxylase (beta cells of the pancreatic islets)- autoimmune diabetes

Lysosomal enzymes (phagocytic cells)- systemic vasculitis

Mitochondrial enzymes (pyruvate dehydrogenase)- primary biliary cirrhosis

Question 19

Give some examples of intracellular molecules that are involved in trancription and translation?

Answer 19

Double stranded DNA, Histones- SLE
Topoisomerase I- Diffuse scleroderma
Amino- acetly t-RNA synthases- polymositis
Centromere proteins- limited scleroderma

Question 20

What contributes to an increasing risk of developing SLE?

Answer 20

Inheritance of HLA-DR2
Inheritance f impaired DNA clearance
Infection leading to apoptosis and interferon secretion
Drugs that reduce DNA clearance
Unknown mechanisms
Exposure to UV light
Pregnancy

Question 21

How do you treat autoimmune disease?

Answer 21

Suppress damaging immune response ( steroids, immuno-therapy)

Replace the function of the damaged organ (TSH, insulin administration)